Hydrochloric Acid → HCID 21093992, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-4-(ethylsulfonyl)benzene (1.50 g) in 1,4-dioxane (20 mL) were added diethyl malonate (1.16 g), potassium phosphate (3.84 g), biphenyl-2-yl(di-tert-butyl)phosphine (108 mg) and palladium acetate (II) (40 mg). The reaction solution was purged with argon, and the mixture was heated under reflux for 12 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-50:50, volume ratio) to give a colorless oil. A solution of the obtained oil in N,N-dimethylformamide (20 mL) was purged with nitrogen, sodium hydride (60%, oil, 213 mg) was added under ice-cooling, and the mixture was stirred at 0° C. for 15 min. To the reaction solution was added a solution of 4-(iodomethyl)tetrahydro-2H-pyran (1.15 g) in N,N-dimethylformamide (10 mL) at 0° C., and the mixture was stirred for 3 hr at 90° C. The reaction mixture was concentrated under reduced pressure, saturated aqueous ammonium chloride solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=10:90-40:60, volume ratio) to give a colorless oil. To a solution of the obtained oil in a mixed solvent of tetrahydrofuran (40 mL) and methanol (20 mL) was added 2M aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at 60° C. for 3 hr. The reaction solution was cooled to room temperature, and acidified with 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from hexane-ethyl acetate to give the title compound (1.33 g, yield 67%) as colorless crystals. MS: 327 (MH+).

Provenance & Evidence